9-133258323-A-G

Variant names:

• chr9-133258323-A-G
• rs641943
• ENST00000611156.4:c.204-191T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000611156.4(ABO):​c.204-191T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,108 control chromosomes in the GnomAD database, including 6,849 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6849 hom., cov: 33)
• Consequence: ABO ENST00000611156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• Publications: 19 publications found

Genes affected

ABO (HGNC:79): (ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase) This gene encodes proteins related to the first discovered blood group system, ABO. Variation in the ABO gene (chromosome 9q34.2) is the basis of the ABO blood group, thus the presence of an allele determines the blood group in an individual. The 'O' blood group is caused by a deletion of guanine-258 near the N-terminus of the protein which results in a frameshift and translation of an almost entirely different protein. Individuals with the A, B, and AB alleles express glycosyltransferase activities that convert the H antigen into the A or B antigen. Other minor alleles have been found for this gene. [provided by RefSeq, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NR_198898.1	n.216-191T>C		intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4	c.204-191T>C		intron_variant	Intron 4 of 7	5		ENSP00000483265.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44638 AN: 151990 Hom.: 6836 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.280

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.294 AC: 44682 AN: 152108 Hom.: 6849 Cov.: 33 AF XY: 0.292 AC XY: 21697 AN XY: 74378

African (AFR) AF: 0.343 AC: 14222 AN: 41480

American (AMR) AF: 0.406 AC: 6199 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 972 AN: 3466

East Asian (EAS) AF: 0.276 AC: 1426 AN: 5170

South Asian (SAS) AF: 0.223 AC: 1073 AN: 4822

European-Finnish (FIN) AF: 0.195 AC: 2063 AN: 10598

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17922 AN: 67980

Other (OTH) AF: 0.279 AC: 589 AN: 2114

Alfa AF: 0.283 Hom.: 3054

Bravo AF: 0.316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.84
PhyloP100		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs641943; hg19: chr9-136133714;